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Confirmation of ALDH2 as a Major Locus of Drinking Behavior and of Its Variants Regulating Multiple Metabolic Phenotypes in a Japanese Population
Open accessAbstract
BACKGROUND: Normative alcohol use (or drinking behavior) influences the risk of cardiovascular disease in a multi-faceted manner. To identify susceptibility gene variants for drinking behavior, a 2-staged genome-wide association study was performed in a Japanese population. METHODS AND RESULTS: In the stage-1 scan, 733 cases and 729 controls were genotyped with 456,827 SNP markers. The associated loci without redundancy of linkage disequilibrium were further examined in the stage-2 general population panel comprising 2,794 drinkers (≥ once per week), 1,521 chance drinkers (< once per week), and 1,351 non-drinkers. Along with genome-wide exploration, we aimed to replicate the trait association of a candidate gene SNP previously reported (rs1229984 in ADH1B). A cluster of 12 SNPs on 12q24 were found to significantly (P<5×10(-8)) associate with drinking behavior in stage 1, among which rs671 (a Glu-to-Lys substitution at position 504) in the ALDH2 gene showed the strongest association (odds ratio (OR)=0.16, P=3.6×10(-211) in the joint analysis). The association was also replicated for rs1229984 (OR=1.20, P<3.6×10(-4)). Furthermore, ALDH2 504Lys was associated with several metabolic traits, eg, lower levels of high-density lipoprotein cholesterol and liver enzymes-AST, ALT, and γGTP-by interacting with alcohol intake. CONCLUSIONS: Our results confirm ALDH2 as a major locus regulating drinking behavior in the Japanese, indicating that the ALDH2 504Lys variant exerts pleiotropic effects on risk factors of cardiovascular disease among drinkers.
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PLINK: a tool set for whole-genome association and population-based linkage analyses.
Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M. A. R., Bender, D., Maller, J., Sklar, P., de Bakker, P. I. W., Daly, M. J., et al. (2007) · The American Journal of Human Genetics · doi:10.1086/519795 · Cited by 34,089
Genomic Control for Association Studies
Devlin, B., & Roeder, K. (1999) · Biometrics · doi:10.1111/j.0006-341x.1999.00997.x · Cited by 3,162
A Map of Recent Positive Selection in the Human Genome
Voight, B. F., Kudaravalli, S., Wen, X., & Pritchard, J. K. (2006) · PLoS Biology · doi:10.1371/journal.pbio.0040072 · Cited by 2,925
Rimm, E. B., Williams, P., Fosher, K., Criqui, M., & Stampfer, M. J. (1999) · BMJ · doi:10.1136/bmj.319.7224.1523 · Cited by 1,360
Skol, A. D., Scott, L. J., Abecasis, G. R., & Boehnke, M. (2006) · Nature Genetics · doi:10.1038/ng1706 · Cited by 1,286
Gaziano, J. M., Buring, J. E., Breslow, J. L., Goldhaber, S. Z., ROSNER, B. A., VanDenburgh, M., Willett, W. C., & Hennekens, C. H. (1993) · New England Journal of Medicine · doi:10.1056/nejm199312163292501 · Cited by 1,012
Activation of Aldehyde Dehydrogenase-2 Reduces Ischemic Damage to the Heart
Chen, C., Budas, G. R., Churchill, E. N., Disatnik, M., Hurley, T. D., & Mochly‐Rosen, D. (2008) · Science · doi:10.1126/science.1158554 · Cited by 766
Effects of Alcohol Reduction on Blood Pressure: A Meta-Analysis of Randomized Controlled Trials
Xin, X., He, J., Frontini, M. G., Ogden, L. G., Motsamai, O. I., & Whelton, P. K. (2001) · Hypertension · doi:10.1161/hy1101.093424 · Cited by 738
Signals of recent positive selection in a worldwide sample of human populations
Pickrell, J. K., Coop, G., Novembre, J., Kudaravalli, S., Li, J. Z., Absher, D., Srinivasan, B. S., Barsh, G. S., Myers, R. M., Feldman, M. W., et al. (2009) · Genome Research · doi:10.1101/gr.087577.108 · Cited by 717
Moderate Alcohol Consumption Lowers the Risk of Type 2 Diabetes
Koppes, L. L. J., Dekker, J. M., Hendriks, H. F. J., Bouter, L. M., & Heine, R. J. (2005) · Diabetes Care · doi:10.2337/diacare.28.3.719 · Cited by 671
Soranzo, N., Spector, T. D., Mangino, M., Kuehnel, B., Rendon, A., Teumer, A., Willenborg, C., Wright, B. J., Chen, L., Li, M., et al. (2009) · Nature Genetics · doi:10.1038/ng.467 · Cited by 527
A genome-wide association study of alcohol dependence
Bierut, L. J., Agrawal, A., Bucholz, K. K., Doheny, K. F., Laurie, C., Pugh, E., Fisher, S., Fox, L., Howells, W., Bertelsen, S., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0911109107 · Cited by 457
Light-to-Moderate Alcohol Consumption and the Risk of Stroke among U.S. Male Physicians
Berger, K., Ajani, U. A., Kase, C. S., Gaziano, J. M., Buring, J. E., Glynn, R. J., & Hennekens, C. H. (1999) · New England Journal of Medicine · doi:10.1056/nejm199911183412101 · Cited by 358
Refined Geographic Distribution of the Oriental ALDH2*504Lys (nee 487Lys) Variant
Li, H., Borinskaya, S. A., Yoshimura, K., Kal’ina, N. R., Marusin, A. V., Степанов, В. А., Qin, Z., Khaliq, S., Lee, M., Yang, Y., et al. (2009) · Annals of Human Genetics · doi:10.1111/j.1469-1809.2009.00517.x · Cited by 293
Rose, R. J., Dick, D. M., Viken, R. J., & Kaprio, J. A. (2001) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2001.tb02261.x · Cited by 241
Harada, S., Misawa, S., Agarwal, D. P., & Hw, G. (1980) · Europe PMC (PubMed Central) · Cited by 237
Takeuchi, F., Serizawa, M., Yamamoto, K., Fujisawa, T., Nakashima, E., Ohnaka, K., Ikegami, H., Sugiyama, T., Katsuya, T., Miyagishi, M., et al. (2009) · Diabetes · doi:10.2337/db08-1494 · Cited by 235
Self-citationAlkerwi, A., Boutsen, M., Vaillant, M., Barré, J., Lair, M., Albert, A., Guillaume, M., & Dramaix, M. (2008) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2008.10.036 · Cited by 198
Blood Pressure and Hypertension Are Associated With 7 Loci in the Japanese Population
Takeuchi, F., Isono, M., Katsuya, T., Yamamoto, K., Yokota, M., Sugiyama, T., Nabika, T., Fujioka, A., Ohnaka, K., Asano, H., et al. (2010) · Circulation · doi:10.1161/circulationaha.109.904664 · Cited by 195
Self-citationMacGregor, S., Lind, P. A., Bucholz, K. K., Hansell, N. K., Madden, P. A. F., Richter, M. M., Montgomery, G. W., Martin, N. G., Heath, A. C., & Whitfield, J. B. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn372 · Cited by 194
Oota, H., PAKSTIS, A. J., Bonné, B., Goldman, D. A., Grigorenko, E. L., Kajuna, S. L. B., Karoma, N. J., Kungulilo, S., Lu, R., Odunsi, K. O., et al. (2004) · Annals of Human Genetics · doi:10.1046/j.1529-8817.2003.00060.x · Cited by 186
Population genetic studies on aldehyde dehydrogenase isozyme deficiency and alcohol sensitivity.
GOEDDE, H. W., Agarwal, D. P., Harada, S., Meier-Tackmann, D., Ruofu, D., Bienzle, U., Kroeger, A., & Hussein, L. (1983) · Europe PMC (PubMed Central) · Cited by 134
Alcohol and high-density lipoprotein cholesterol: causal inference from diverse study designs.
Hulley, S. B., & Gordon, S. (1981) · PubMed · Cited by 113
Chen, Y.-C., Peng, G., Wang, M.-F., Tsao, T., & Yin, S. (2008) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2008.10.029 · Cited by 106
Linneberg, A. R., González‐Quintela, A., Vidal, C., Jørgensen, T., Fenger, M., Hansen, T. F., Pedersen, O. B., & Husemoen, L. L. N. (2009) · Clinical & Experimental Allergy · doi:10.1111/j.1365-2222.2009.03398.x · Cited by 77
REVIEW: Human and laboratory rodent low response to alcohol: is better consilience possible?
Crabbe, J. C., Bell, R. L., & Ehlers, C. L. (2010) · Addiction Biology · doi:10.1111/j.1369-1600.2009.00191.x · Cited by 75
Nakamura, Y., Amamoto, K., Tamaki, S., Okamura, T., Tsujita, Y., Ueno, Y., Kita, Y., Kinoshita, M., & Ueshima, H. (2002) · Atherosclerosis · doi:10.1016/s0021-9150(02)00059-x · Cited by 64
Influence of ADH1B polymorphism on alcohol use and its subjective effects in a Jewish population
Carr, L. G., Foroud, T., Stewart, T. R., Castelluccio, P., Edenberg, H. J., & Li, T. (2002) · American Journal of Medical Genetics · doi:10.1002/ajmg.10674 · Cited by 57
Biological markers for increased risk of alcoholism and for quantitation of alcohol consumption.
Crabb, D. W. (1990) · Journal of Clinical Investigation · doi:10.1172/jci114439 · Cited by 54
Kato, I. (2003) · Journal of Clinical Epidemiology · doi:10.1016/s0895-4356(02)00578-4 · Cited by 50
Tsuchihashi‐Makaya, M., Serizawa, M., Yanai, K., Katsuya, T., Takeuchi, F., Fujioka, A., Yamori, Y., Ogihara, T., & Kato, N. (2009) · Hypertension Research · doi:10.1038/hr.2009.3 · Cited by 46
Self-citationWada, M., Daimon, M., Emi, M., Iijima, H., Sato, H., Koyano, S., Tajima, K., Kawanami, T., Kurita, K., Hunt, S. C., et al. (2008) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.e542 · Cited by 33
The ALDH2 genotype, alcohol intake, and liver-function biomarkers among Japanese male workers
Takeshita, T., Yang, X. H., & Morimoto, K. (2000) · Human Genetics · doi:10.1007/s004390000314 · Cited by 33
Effects of 5-week ethanol feeding on the liver of aldehyde dehydrogenase 2 knockout mice
Matsumoto, A., Kawamoto, T., 武藤, 文., Isse, T., Oyama, T., Kitagawa, K., Nakayama, K. I., & Ichiba, M. (2008) · Pharmacogenetics and Genomics · doi:10.1097/fpc.0b013e328307a0a9 · Cited by 26
Evaluation of Pharmacogenetic Algorithm for Warfarin Dose Requirements in Japanese Patients
Takeuchi, F., Kashida, M., Okazaki, O., Tanaka, Y., Fukuda, S., Kashima, T., Hosaka, S., Hiroe, M., Kimura, S., & Kato, N. (2010) · Circulation Journal · doi:10.1253/circj.cj-09-0876 · Cited by 26
Self-citationHiura, Y., Tabara, Y., Kokubo, Y., Okamura, T., Goto, Y., Nonogi, H., Miki, T., Tomoike, H., & Iwai, N. (2010) · Circulation Journal · doi:10.1253/circj.cj-09-0790 · Cited by 21
What Aspects of Human Alcohol Use Disorders Can Be Modeled Using Selectively Bred Rat Lines?
Froehlich, J. C. (2010) · Substance Use & Misuse · doi:10.3109/10826084.2010.482424 · Cited by 13
Yamada, Y., Imai, T., Ishizaki, M., & Honda, R. (2005) · Journal of Human Genetics · doi:10.1007/s10038-005-0330-0 · Cited by 11
The ALDH2 genotype, alcohol intake, and liver-function biomarkers among Japanese male workers
Takeshita, T., Yang, X., & Morimoto, K. (2000) · Human Genetics · doi:10.1007/s004390050029 · Cited by 7
Brown, B. T., Woerner, A. E., & Wilder, J. A. (2007) · Journal of Molecular Evolution · doi:10.1007/s00239-006-0149-0 · Cited by 3
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Genetic architectures of psychiatric disorders: the emerging picture and its implications
Sullivan, P. F., Daly, M. J., & O'Donovan, M. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3240 · Cited by 1,177
Psychiatric Genomics: An Update and an Agenda
Sullivan, P. F., Agrawal, A., Bulik, C. M., Andreassen, O. A., Børglum, A. D., Breen, G., Cichon, S., Edenberg, H. J., Faraone, S. V., Gelernter, J., et al. (2018) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2017.17030283 · Cited by 676
Kato, N., Takeuchi, F., Tabara, Y., Kelly, T. N., Go, M. J., Sim, X., Tay, W. T., Chen, C.-H., Zhang, Y., Yamamoto, K., et al. (2011) · Nature Genetics · doi:10.1038/ng.834 · Cited by 571
Self-citationKranzler, H. R., Zhou, H., Kember, R. L., Vickers‐Smith, R., Justice, A. C., Damrauer, S. M., Tsao, P. S., Klarin, D. M., Baras, A., Reid, J. G., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09480-8 · Cited by 482
Goodarzi, M. O. (2017) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(17)30200-0 · Cited by 503
Metadata
- Authors
- Takeuchi, F., Isono, M., Nabika, T., Katsuya, T., Sugiyama, T., Yamaguchi, S., Kobayashi, S., Ogihara, T., Yamori, Y., Fujioka, A., & Kato, N.
- Affiliations
- National Center for Global Health and Medicine (JP)
- Shimane University (JP)
- The University of Osaka (JP)
- The Institute of Medical Science, Asahi Life Foundation (JP)
- Shimane University Hospital (JP)
- Osaka Prefectural Medical Center (JP)
- Mukogawa Women's University (JP)
- Amagasaki Health Medical Foundation
- ORCID
- Venue
- Circulation Journal
- Publisher
- Japanese Circulation Society
- Published
- 2011
- Volume
- 75
- Issue
- 4
- Pages
- 911-918
- ISSN
- 1346-9843 (ISSN-L)
- 1347-4820
- OpenAlex
- W2038050993
- Cited by
- 146
- References
- 39
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 10 · 2023: 7 · 2022: 9 · 2021: 16 · 2020: 10 · 2019: 12 · 2018: 11 · 2017: 16 · 2016: 11 · 2015: 9 · 2014: 13 · 2013: 10 · 2012: 5
- FWCI
- 6.51
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation Journal (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Funders
- National Center for Global Health and Medicine
- National Institute of Biomedical Innovation
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Keywords
- ALDH2, drinking behavior, alcohol consumption, rs671, ADH1B, rs1229984, alcohol metabolism, HDL cholesterol, liver enzymes, cardiovascular risk, pleiotropy, Japanese population
- MeSH terms
- Aldehyde Dehydrogenase, Mitochondrial, Adult, Aged, Aged, 80 and over, Aldehyde Dehydrogenase, Cardiovascular Diseases, Drinking Behavior, Humans, Japan, Male, Middle Aged, Risk Factors, Amino Acid Substitution, Genetic Predisposition to Disease, Mutation, Missense, Polymorphism, Single Nucleotide, Asian People, Genome-Wide Association Study, Genetic Loci
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